Neurodegenerative and neuropsychiatric disorders are two broad categories of neurological disorders characterized by progressive impairments in movement and cognitive functions within the central and peripheral nervous systems, and have emerged as a significant cause of mortality. Oxidative stress, neuroinflammation, and neurotransmitter imbalances are recognized as prominent pathogenic factors contributing to cognitive deficits and neurobehavioral anomalies. Consequently, preventing neurodegenerative and neuropsychiatric diseases has surfaced as a pivotal challenge in contemporary public health. This review explores the investigation of neurodegenerative and neuropsychiatric disorders using both synthetic and natural bioactive compounds. A central focus lies on melatonin, a neuroregulatory hormone secreted by the pineal gland in response to light-dark cycles. Melatonin, an amphiphilic molecule, assumes multifaceted roles, including scavenging free radicals, modulating energy metabolism, and synchronizing circadian rhythms. Noteworthy for its robust antioxidant and antiapoptotic properties, melatonin exhibits diverse neuroprotective effects. The inherent attributes of melatonin position it as a potential key player in the pathophysiology of neurological disorders. Preclinical and clinical studies have demonstrated melatonin's efficacy in alleviating neuropathological symptoms across neurodegenerative and neuropsychiatric conditions (depression, schizophrenia, bipolar disorder, and autism spectrum disorder). The documented neuroprotective prowess of melatonin introduces novel therapeutic avenues for addressing neurodegenerative and psychiatric disorders. This comprehensive review encompasses many of melatonin's applications in treating diverse brain disorders. Despite the strides made, realizing melatonin's full neuroprotective potential necessitates further rigorous clinical investigations. By unravelling the extended neuroprotective benefits of melatonin, future studies promise to deepen our understanding and augment the therapeutic implications against neurological deficits.